Screening for Lysosomal Acid Lipase Deficiency

SCREENING FOR LYSOSOMAL ACID LIPASE DEFICIENCY AS THE UNDERLYING SOURCE OF HEPATIC INJURY IN PEDIATRIC PATIENTS WITH EVIDENCE OF ABNORMAL CLINICAL OR BIOCHEMICAL TESTS (DETECT)

The primary outcome of this study is the development of a clinical profile of pediatric patients with LAL-D, which will enable the Sponsor to provide more focused guidance to the medical community as to which pediatric patients should be tested for LAL-D.

Inclusion Criteria:

1. Male or female patient is ≥ 2 to ≤ 16 years of age at the date of informed consent. (Note: Female patients who are of childbearing potential or are pregnant may participate in this study.)
2. Patient or patient's parent or legal guardian (if applicable) consents to participation in the study. If the patient is of minor age, he/she is willing to provide assent where required per local regulations, and if deemed able to do so.
3. Patient meets all components of Criterion A and/or Criterion B below.

Criterion A: Patient has dyslipidemia, defined as having at least one of the following lipid abnormalities based on a local laboratory result obtained within 3 months prior to the date of informed consent (or at the screening visit, as applicable):

LDL-c ≥ 130 mg/dL HDL c ≤ 40 mg/dL (male patients) or ≤ 50 mg/dL (female patients) Note: For patients receiving a lipid-lowering medication (LLM), the patient must have been on a stable dose of the LLM for at least 4 weeks prior to the serum lipid result.

AND

Patient has at least one of the following liver or spleen abnormalities:

Hepatomegaly, as determined by the investigator based on a physical examination or imaging procedure; Splenomegaly, as determined by the investigator based on a physical examination or imaging procedure; ALT >75 U/L or ALT >1.5x the upper limit of normal (ULN) (based on age- and gender-specific normal ranges of the local laboratory performing the assay) within 3 months prior to the date of informed consent (or at the screening visit, as applicable).

Criterion B: Patient has steatosis (microvesicular or mixed macro/microvesicular), hepatic fibrosis, and/or cirrhosis of unknown etiology, as determined from a liver biopsy performed within the previous 3 years. (Note: For patients who have received a liver transplantation, the liver biopsy results must have been obtained prior to the date of the liver transplantation.)

Exclusion Criteria:

1. Patient has a confirmed cause of liver disease other than LAL-D.
2. Patient has genetically confirmed heterozygous familial hypercholesteremia or other secondary causes of hypercholesterolemia.
3. Patient has current evidence of neurological dysfunction and/or a history of neurological dysfunction within one year prior to the date of informed consent.
4. Patient has been previously screened for LAL-D and found to have normal enzyme activity based on the reference range of the laboratory performing the assay.
5. Patient is currently receiving treatment with sebelipase alfa (Kanuma) or has previously participated in a clinical study with sebelipase alfa (Kanuma).